Clinical Characteristics of Pathogenic ACAN Variants and 3-Year Response to Growth Hormone Treatment: Real-World Data.

INTRODUCTION: Heterozygous variants in the ACAN gene may underlie disproportionate short stature with characteristically accelerated bone age (BA) maturation and/or early-onset osteoarthritis (OA). METHODS: The objective of this study was to describe phenotype, analyze genotype-phenotype correlations, and assess the response of growth hormone (GH) treatment in children with a heterozygous ACAN variant. Thirty-six subjects (23 boys, 13 girls) with ACAN deficiency and treated for ≥1 year with GH were identified in the Dutch National Registry of GH treatment in children. RESULTS: We identified 25 different heterozygous ACAN variants in 36 subjects. Median (interquartile range) height SDS at start of GH was -2.6 SDS (-3.2 to -2.2). Characteristic features such as disproportion, advanced BA, early-onset OA, and dysmorphic features like midface hypoplasia and brachydactyly were present in the majority of children, but in ∼20%, no specific features were reported. Subjects with a truncating ACAN variant had a shorter height SDS compared to subjects with a non-truncating variant (-2.8 SDS and -2.1 SDS, respectively, p = 0.002). After 3 years of GH, height gain SDS in prepubertal children was 1.0 SDS (0.9-1.4). In pubertal children, height SDS remained relatively stable. CONCLUSION: The phenotype of subjects with pathogenic heterozygous ACAN variants is highly variable, and genetic testing for ACAN deficiency should be considered in any child with significant short stature, even in the absence of disproportion, specific dysmorphic features, or BA advancement. Furthermore, children with ACAN deficiency may benefit from GH with a modest but significant response, which is sustained during 3 years of treatment.

Progress against non-Hodgkin's lymphoma in children and young adolescents in the Netherlands since 1990: Stable incidence, improved survival and lower mortality.

BACKGROUND: With epidemiologic analyses of population-based trends in incidence and outcomes, we ascertained progress against non-Hodgkin's lymphoma (NHL) in children and young adolescents in the Netherlands since 1990. METHODS: Tumour characteristics were extracted from the Netherlands Cancer Registry for patients aged <18 years at diagnosis, between 1990 and 2015. Mortality data for 1980-2016 were derived from Statistics Netherlands. NHL subtypes comprised lymphoblastic lymphoma (LBL), Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL) and anaplastic large cell lymphoma (ALCL). Time trends in incidence and mortality rates and 5-year overall survival (OS) rates were evaluated by average annual percentage change (AAPC) analyses and parametric survival models, respectively. RESULTS: Overall incidence of NHL remained stable at 11 per million person-years (AAPC -0.2%, p = 0.68), with a marked decrease among children of 5-9 years (AAPC -2.6%, p < 0.01), especially among those with BL. Treatment regimens comprised less radiotherapy over time, especially for LBL and BL. Since 2004, most 15-17-year-old patients with NHL have been treated at a paediatric oncology centre. Five-year OS improved from 71% in 1990-94 to 87% in 2010-15 (p < 0.01), the most gain has been achieved in patients with DLBCL and ALCL from 60% and 73%, respectively, to both 90%. Population-based mortality from NHL decreased significantly towards 1.4 per million person-years (AAPC -4.2%, p < 0.01). CONCLUSIONS: This population-based epidemiological study exhibited significant progress against childhood and young adolescent NHL in the Netherlands since 1990, before the advent of a national paediatric oncologic centre in 2018: incidence decreased among children of 5-9 years, survival improved, and mortality steadily decreased over time.

Significant improvement in survival of advanced stage childhood and young adolescent cancer in the Netherlands since the 1990s.

BACKGROUND: This is the first national study on trends in cancer survival and mortality for children and young adolescents in the Netherlands including unique information on stage at diagnosis. METHODS: All neoplasms in patients <18 years, diagnosed between 1990 and 2015 (N = 14,060), were derived from the Netherlands Cancer Registry. Cohort and period survival analyses were used to estimate observed survival (OS). Time trends in OS and mortality rates were evaluated by parametric survival models and average annual percentage change, respectively. RESULTS: Between 1990 and 2015, 5-year OS and 10-year OS of childhood and young adolescent cancer have improved significantly by 9 percent points, reaching 81% and 78%, respectively. Favourable trends in survival were observed for all age groups and most diagnostic (sub)groups, being particularly pronounced for advanced disease. Non-Hodgkin lymphomas Ann Arbor stage III, metastatic neuroblastomas (age ≥18 months) and Ewing bone sarcomas showed significant improvements in 5-year OS. Compared with 1990-99, the risk of dying within five years of diagnosis was decreased significantly during 2000-09 (hazard ratio [HR] = 0.8) and 2010-15 (HR = 0.6), after adjustment for age, gender and follow-up time. Nonetheless, the prognosis of young patients suffering from central nervous system tumours, neuroblastoma and osteosarcomas remained modest, with 5-year OS <70% and 10-year OS <65%. Childhood and young adolescent cancer mortality decreased by an average of 2.0% annually between 1990 and 2018. CONCLUSIONS: Significant progress has been realised in the prognosis of childhood and young adolescent cancer in the Netherlands since the 1990s. Survival improvements were especially evident for patients with advanced stages and were also reflected in the declining mortality rates.

Progress against childhood and adolescent acute lymphoblastic leukaemia in the Netherlands, 1990-2015.

We assessed the epidemiologic progress against childhood and adolescent acute lymphoblastic leukaemia (ALL) in the Netherlands over a 26 year period. ALL patients <18 years were selected from the Netherlands Cancer Registry and the Dutch Childhood Oncology Group. Trend analyses were performed over time and by age group and ALL subtype. Between 1990 and 2015, 2997 ALL patients were diagnosed, i.e. 115 patients (range 87-147) per year. Overall incidence remained stable at 37 per million children, despite increases for B-cell precursor ALL (BCP-ALL) at age 10-14 years (AAPC + 1.4%, p = 0.04) and T-cell ALL at 15-17 years (AAPC + 3.7%, p = 0.01). Five-year survival increased from 80% in 1990-94 to 91% in 2010-15 (p < 0.01). Mortality decreased by 4% annually (p < 0.01). Patients 15-17 years were increasingly treated in a paediatric oncology centre, from 35% in 1990-94 to 87% in 2010-15 and experienced a 70% reduction of risk of death compared to those treated outside such a centre (p < 0.01). Significant progress against childhood ALL has been made in the Netherlands, visible by improved survival rates coinciding with declining mortality rates. These outcomes were accompanied by stable incidence rates, despite increases for BCP-ALL at age 10-14 years and T-cell ALL at age 15-17 years.

Increasing incidence of cancer and stage migration towards advanced disease in children and young adolescents in the Netherlands, 1990-2017.

BACKGROUND: This is the first national study on trends in cancer incidence for children and young adolescents in the Netherlands, including stage at diagnosis as a potential marker of early diagnosis and better staging. METHODS: All neoplasms in patients younger than 18 years, diagnosed between 1990 and 2017 (N = 15,233), were derived from the Netherlands Cancer Registry. Incidence rates and the average annual percentage change with 95% CIs were calculated for all cancers combined and diagnostic (sub)groups. The stability of trends was examined by joinpoint analyses. Potential changes in early detection or improved staging over time were evaluated through proportional alterations in stage at diagnosis. RESULTS: The annual overall cancer incidence increased significantly over time by 0.6% (95% CI 0.3-0.8) from 144 per million person-years in 1990-1999 to 162 in 2010-2017 and was significant for both boys (+0.5%, 0.2-0.8) and girls (+0.7%, 0.3-1.1), for infants (aged 0 years; +1.5%, 0.4-2.5), teenagers (aged 10-14 years; +0.6%, 0.3-1.0) and young adolescents (aged 15-17 years; +0.7%, 0.2-1.2), with no trend interruptions. The incidence of leukaemia (+0.7%, 0.3-1.2), malignant CNS tumours including pilocytic astrocytomas (+1.0%, 0.5-1.5), neuroblastoma (+1.2%, 0.1-2.2) and Ewing bone tumours (+2.4%, 0.9-4.0) increased significantly, whereas temporal variation in trends was observed in boys diagnosed with leukaemia, in pilocytic astrocytoma and malignant melanoma. The proportion of early-stage disease increased in patients with testicular germ cell tumours (+21%) and malignant melanomas (+14%), whereas stage migration towards advanced disease was seen for Hodgkin lymphomas, soft tissue sarcomas and medullary thyroid carcinomas. CONCLUSION: The increasing childhood cancer incidence could not be explained by a rise in early diagnosis, which suggests that background risk factors seem of more importance.

Improved survival for adolescents and young adults with Hodgkin lymphoma and continued high survival for children in the Netherlands: a population-based study during 1990-2015.

Population-based studies that assess long-term patterns of incidence, major aspects of treatment and survival are virtually lacking for Hodgkin lymphoma (HL) at a younger age. This study assessed the progress made for young patients with HL (<25 years at diagnosis) in the Netherlands during 1990-2015. Patient and tumour characteristics were extracted from the population-based Netherlands Cancer Registry. Time trends in incidence and mortality rates were evaluated with average annual percentage change (AAPC) analyses. Stage at diagnosis, initial treatments and site of treatment were studied in relation to observed overall survival (OS). A total of 2619 patients with HL were diagnosed between 1990 and 2015. Incidence rates increased for 18-24-year-old patients (AAPC + 1%, P = 0·01) only. Treatment regimens changed into less radiotherapy and more 'chemotherapy only', different for age group and stage. Patients aged 15-17 years were increasingly treated at a paediatric oncology centre. The 5-year OS for children was already high in the early 1990s (93%). For patients aged 15-17 and 18-24 years the 5-year OS improved from 84% and 90% in 1990-1994 to 96% and 97% in 2010-2015, respectively. Survival for patients aged 15-17 years was not affected by site of treatment. Our present data demonstrate that significant progress in HL treatment has been made in the Netherlands since 1990.

Treatment-related mortality in children with cancer: Prevalence and risk factors.

AIM: Intensive treatment regimens have contributed to a marked increase in childhood cancer survival rates. Death due to treatment-related adverse effects becomes an increasingly important area to further improve overall survival. In this study, we examined 5-year survival in children with cancer to identify risk factors for treatment-related mortality (TRM). METHODS: All children (aged <18 years at diagnosis) diagnosed with cancer in 2 Dutch university hospitals between 2003 and 2013 were included, survival status was determined and causes of death were analysed. Various demographic and treatment factors were evaluated, for which a multivariable competing risks analysis was performed. RESULTS: A total of 1764 patients were included; overall 5-year survival was 78.6%. Of all 378 deaths, 81 (21.4%) were treatment-related, with infection being responsible for more than half of these deaths. Forty percent of TRM occurred in the first three months after initial diagnosis. Factors associated with TRM in the multivariable competing risks analysis were diagnosis of a haematological malignancy, age at diagnosis <1 year and receipt of allogeneic haematopoietic stem cell transplantation. In children suffering from haematological malignancies, TRM accounted for 56.3% of 103 deaths. CONCLUSION: Over one in five deaths in children with cancer death was related to treatment, mostly due to infection. In children suffering from a haematological malignancy, more children died due to their treatment than due to progression of their disease. To further increase overall survival, clinical and research focus should be placed on lowering TRM rates without compromising anti-tumour efficacy. The findings presented in this study might help identifying areas for improvement.

Characteristics and outcome in patients with central nervous system involvement treated in European pediatric acute myeloid leukemia study groups.

BACKGROUND: There is no consensus on the treatment for pediatric patients with acute myeloid leukemia and initial central nervous system (CNS) involvement. METHODS: To evaluate different CNS-directed treatment options (intrathecal [IT] therapy, CNS irradiation, hematopoietic stem cell transplantation [HSCT]), 261 patients (excluding acute promyelocytic leukemia) with initial CNS involvement treated in trials with similar intensive chemotherapy by four cooperative European study groups (1998-2013) were studied and compared with CNS-negative patients from the Berlin-Frankfurt-Münster group. RESULTS: Patient characteristics in the different study groups were comparable. Young age, high white blood cell count, extramedullary involvement other than the CNS, monoblastic morphology, and inv(16) were associated with CNS involvement (each P < 0.0001). There were no major differences in outcome between the study groups. The cumulative incidence of relapse (CIR) regarding the CNS was higher in initially CNS-positive versus initially CNS-negative patients (all: 8 ± 2% vs. 3 ± 1%, P(Gray) = 0.001; isolated: 4 ± 1% vs. 1 ± 0%, P(Gray) = 0.03). However, global outcome of the CNS-positive cohort (overall survival, 64 ± 3%; event-free survival 48 ± 3%; and CIR 33% ± 3%) did not differ significantly from CNS-negative patients. Risk groups defined by cytogenetics were of likewise prognostic significance in CNS-positive and -negative patients. CNS treatment with cranial irradiation was not superior compared to IT therapy and systemic chemotherapy (± HSCT). CONCLUSION: Although CNS relapses occurred more frequently in initially CNS-positive patients, their global outcome was similar as in CNS-negative patients. Intensified IT therapy was heterogeneous; however, at least eight applications, preferably with triple IT chemotherapy, seem to be appropriate to accompany dose-intensive systemic chemotherapy.

Prospective neoadjuvant analysis of PET imaging and mechanisms of resistance to Trastuzumab shows role of HIF1 and autophagy.

BACKGROUND: Although Trastuzumab has improved survival of HER2+ breast cancer patients, resistance to the agent pre-exists or develops through the course of therapy. Here we show that a specific metabolism and autophagy-related cancer cell phenotype relates to resistance of HER2+ breast cancer to Trastuzumab and chemotherapy. METHODS: Twenty-eight patients with locally advanced primary breast cancer were prospectively scheduled to received one cycle of Trastuzumab followed by a new biopsy on day 21, followed by taxol/Trastuzumab chemotherapy for four cycles before surgery. FDG PET/CT scan was used to monitor tumour response. Tissue samples were immunohistochemically analysed for metabolism and autophagy markers. RESULTS: In pre-Trastuzumab biopsies, the LC3A+/HER2+ cell population was correlated with HIF1α expression (P=0.01), while GLUT1 and LC3B expression were correlated with Ki67 proliferation index (P=0.01 and P=0.01, respectively). FDG PET tumour dimensions before therapy were correlated with LC3B expression (P=0.005). Administration of Trastuzumab significantly reduced clinical and PET-detected tumour dimensions (P<0.01). An inverse association of tumour response with the percentage of cells expressing HIF1α at baseline was documented (P=0.01). Administration of Trastuzumab resulted in a decrease of the proliferation index (P=0.004), GLUT1 (P=0.04) and HER2 (P=0.01) expression. In contrast, the percentage of LC3A+/HER2+ cells was increased (P=0.01). High baseline HIF1α expression was the only parameter associated with poorer pathological response to preoperative chemotherapy (P=0.001). CONCLUSIONS: As the HER2+/LC3A+ phenotype, which often overexpresses HIF1α, is a major subpopulation increasing after therapy with Trastuzumab, LC3A- and HIF1α-targeting therapies should be investigated for the augmentation of anti-HER2 therapy efficacy.

[Childhood leukaemia in a residential area with a high-voltage power line: approach according to the Dutch Community Health Services' guideline 'Cancer Clusters']. / Kinderleukemie in een wijk met een hoogspanningslijn: aanpak volgens de GGD-richtlijn 'Kankerclusters'.

The new Dutch Community Health Services' (GGD) guideline titled 'Cancer Clusters' describes a phased plan for investigating reported cancer clusters. In each phase, attention is paid to both health and environmental issues and their possible links to one another. Throughout the entire cluster investigation, good risk communication is essential. In accordance with the new guideline, the Rotterdam-Rijnmond Public Health Services investigated the incidence of childhood leukaemia in a residential area as well as the data available on the high-voltage power line located there. More children in this residential area had been diagnosed with leukaemia than expected. However, the children had not been subjected to prolonged exposure to strong magnetic fields emitted from the high-voltage power line. With this type of cluster investigation, it is not possible to establish a causal relationship between childhood leukaemia and high-voltage power lines. However, the research did provide stakeholders insight into the health-and-environment situation and thereby, the opportunity to assess the situation appropriately and to act accordingly, if desired.

Impact of dental care in the prevention of bisphosphonate-associated osteonecrosis of the jaw: a single-center clinical experience.

BACKGROUND: Osteonecrosis of the jaw (ONJ) is associated with bisphosphonate (BP) therapy and invasive dental care. An Interdisciplinary Care Group (ICG) was created to evaluate dental risk factors and the efficacy of a preventive restorative dental care in the reduction of ONJ risk. PATIENTS AND METHODS: This prospective single-center study included patients with bone metastases from solid tumors. Patients who received at least one BP infusion between October 2005 and 31 August 2009 underwent one or more ICG evaluation and regular dental examinations. We also retrospectively evaluated patients with bone metastases from solid tumors who did not undergo dental preventive measures. RESULTS: Of 269 patients, 211 had received at least one infusion of BP therapy: 62% were BP naive and 38% had previous BP exposure. Of these 211 patients followed for 47 months, 6 patients developed ONJ (2.8%). Of 200 patients included in the retrospective analysis, 11 patients developed ONJ (5.5%). CONCLUSIONS: In comparison with published ONJ rates and those extrapolated from the retrospective analysis, the observed ONJ rate in the prospective group was lower, suggesting that implementation of a preventive dental program may reduce the risk of ONJ in metastatic patients treated with i.v. BP therapy.

Implementation of sentinel node biopsy in breast cancer patients in the Netherlands.

BACKGROUND: This population-based study describes the implementation of the sentinel node biopsy (SNB) in breast cancer patients in the Netherlands. We examined the extent of use over time of SNB in women who were considered eligible for SNB on the basis of their clinical status. METHODS: The study included a total of 35,465 breast cancer patients who were diagnosed with T1-2 tumours (5.0 cm), negative axillary lymph node status and no distant metastases upon clinical examination between 1st January 1998 and 31st December 2003 in six Comprehensive Cancer Centre regions in the Netherlands. Information on axillary surgery was classified as SNB alone, SNB+axillary lymph node dissection (ALND), ALND alone or none. Patterns of use of axillary surgery were summarised as the proportion of patients receiving each surgery type. RESULTS: Overall, 25.7% of patients underwent SNB alone, 19.1% underwent SNB+ALND, 50.0% had ALND alone and 5.2% did not have axillary surgery. SNB was more common in women who had breast-conserving surgery: 50.5% of patients who received breast-conserving surgery underwent SNB compared to 40.7% of patients who had mastectomy (p<0.0001). Amongst patients receiving breast-conserving treatment, 31.7% had SNB as final axillary surgery, whilst 20.5% of patients who had mastectomy had SNB alone (p<0.0001). The proportion of women who underwent a SNB alone or in combination with ALND increased over the period 1998-2003, from 2.1% to 45.8% and from 6.7% to 24.8%, respectively. There were marked differences in the patterns of dissemination of the use of SNB between regions: by 2003, the difference between the regions with the highest and lowest proportion of use was 25%. CONCLUSIONS: SNB has become the standard-of-care for the treatment of breast cancer patients clinically diagnosed with T1-2 tumours, clinically negative lymph nodes and without distant metastases. In 2003, 70.6% of patients with early breast cancer in the Netherlands received SNB, and within this group, 64.9% of patients had SNB as the final axillary treatment. Implementation of SNB may depend on factors associated with regional organisation of care.

Overall survival in the intervention arm of a randomized controlled screening trial for prostate cancer compared with a clinically diagnosed cohort.

OBJECTIVES: This population-based study provides comparisons of prostate cancer characteristics at diagnosis of two cohorts of men from two well-defined geographical areas exposed to different intensities of prostate cancer screening. Overall survival in both cohorts was compared with that in the general population. METHODS: A cohort of 822 men randomized to the intervention arm of a prostate cancer screening trial and subsequently diagnosed with prostate cancer was compared with a nonrandomized cohort of 947 men who were clinically diagnosed with prostate cancer in a geographically neighboring region. In both cohorts, cases were diagnosed with prostate cancer between January 1989 and December 1997. A partitioning of overall survival by variables associated with cancer onset such as age at diagnosis, stage at diagnosis, and grade at diagnosis was performed. RESULTS: Age at diagnosis, tumor extent at diagnosis, and grade at diagnosis were significantly different between the screened and clinically diagnosed cohort. The 5- and 10-yr survival rates were higher in the screened cohort than in the clinically diagnosed cohort (88.8% vs. 52.4%, and 68.4% vs. 29.6%, respectively). Significant differences in survival were evident for all age, stage, and grade subgroups, except for metastatic disease at diagnosis. CONCLUSIONS: Differences in overall survival favoring the screened population were observed for all baseline characteristics (age, stage, and grade of disease), and these variables may all explain differences in overall survival because screening achieves early diagnosis as well as a stage and grade shift. As observed survival rates in the screened population mirrored those within the general population, the contribution of lead time and overdiagnosis to final patient outcome is considered to be large as well.

Weekly cisplatin plus capecitabine in metastatic breast cancer patients heavily pretreated with both anthracycline and taxanes.

BACKGROUND: Treating patients with anthracycline- and taxane-pretreated metastatic breast cancer is challenging. This study evaluated the activity and safety of a combination of cisplatin and capecitabine in this setting. PATIENTS AND METHODS: Thirty-nine consecutive patients entered the study. All had experienced failures or relapse after previous treatment with anthracyclines and taxanes plus/minus other chemotherapeutic regimens. The present treatment consisted of intravenous cisplatin 20 mg/m(2) every week for 6 weeks, followed by 1 week of rest, and oral capecitabine 1,000 mg/m(2) twice daily for 14 days, followed by a 7-day rest period. RESULTS: Objective response was obtained in 14 patients (35.9%), with complete remission in 3 (7.7%). Median time to progression was 5.2 months and survival was 10.9 months in the entire population and 8.7 and 16.5 months in the responding patients, respectively. The dose-limiting toxicity for the regimen was leucopenia, while gastrointestinal discomfort was the most frequent cause of capecitabine reduction or delay. CONCLUSIONS: The cisplatin and capecitabine combination regimen is active and manageable. It seems to be non-cross resistant to anthracyclines and taxanes.

Increasing incidence and improved survival of cancer in children and young adults in Southern Netherlands, 1973-1999.

The aim of this study was to describe time trends in incidence, treatment and survival of children (0-14 years) and young adults (15-24 years) with cancer in an area in the Netherlands with a long registration period. Between 1973 and 1999, the population-based Eindhoven Cancer Registry (ECR) recorded 852 children and 1162 young adults with a malignancy and they were actively followed up until 1 July, 2003. The world standardised incidence rates for both children and young adults showed an increasing trend until 1997 and this flattened off afterwards (estimated annual percentage change [EAPC]=3.1%, P=0.66 for children and EAPC=3.6%, P=0.06 for young adults). Lymphomas in children and testicular malignancies and melanomas in young adults seemed to increase in particular. Better detection probably led to higher completeness for gliomas. Initial treatment for leukaemias and lymphomas in children has changed, protocols prescribe more chemotherapy and less radiotherapy. For all cancers combined, the 10-year survival rate for children significantly improved from 53% (95% confidence interval [95% CI] 45-61%) in 1973-1982 to 75% (95% CI 69-81%) in 1993-1999 (P-value<0.05). The 10-year survival rate for young adults significantly improved from 57% (95% CI 49-65%) to 81% (95% CI 77-85%) (P-value<0.05). We demonstrated significantly higher five-year survival rates for children with Hodgkin's disease (HD) and young adults with HD, non-seminoma or melanoma diagnosed in 1993-1999.

Paclitaxel, vinorelbine and 5-fluorouracil in breast cancer patients pretreated with adjuvant anthracyclines.

We investigated the activity and toxicity of a combination of vinorelbine (VNB), paclitaxel (PTX) and 5-fluorouracil (5-FU) continuous infusion administered as first-line chemotherapy in metastatic breast cancer patients pretreated with adjuvant anthracyclines. A total of 61 patients received a regimen consisting of VNB 25 mg m(-2) on days 1 and 15, PTX 60 mg m(-2) on days 1, 8 and 15 and continuous infusion of 5-FU at 200 mg m(-2) every day. Cycles were repeated every 28 days. Disease response was evaluated by both RECIST and World Health Organization (WHO) criteria. Objective responses were recorded in 39 of 61 patients (64.0%) assessed by WHO and in 36 of 50 patients (72.0%) assessable by RECIST criteria. Complete remission occurred in 15 (24.6%) and 14 patients (28.0%), respectively. The median time to progression and overall survival of entire population was 10.6 and 27.3 months, respectively, and median duration of complete response was 14.8 months. The dose-limiting toxicity was myelosuppression (leucopenia grade 3/4 in 52.5% of patients). Grade 3/4 nonhaematologic toxicities included mucositis/diarrhoea in 13.1%, skin in 3.3% and cardiac in 1.6% of patients. Grade 2/3 neurotoxicity was observed in five patients (7.2%). The VNB, PTX and 5-FU continuous infusion combination regimen was active and manageable. Complete responses were frequent and durable.

Breast cancer cellular proliferation indexes and 99mTc-sesta Mibi capture: what correlation?

Aim of this study was to verify existing correlations between breast cancer 99mTc-sestaMIBI cells uptake and their cytological characteristics. Forty-five patients with clinically and/or mammographically suspect breast cancer were enrolled. In all patients 99mTc-sestaMIBI scintimammography was performed and malignant lesions were detected in 44 cases and benign in one case. In positive uptake (PU) lesions with diameter <1.5cm, 85.7% showed a high tumor grade (II-III degrees) while in negative uptake (NU) lesions with diameter <1.5cm, 100% showed a low tumor grade (I degrees). In PU lesions, 70% had expressed a high value of Ki 67, while 100% of the NU lesions showed normal values. In this series, tumor diameter does not play a basic role, while the correlations between uptake and the histological grade (G) and/or cellular kinetics (Ki67) seem to be more important. Further studies are needed to confirm our present results.